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Effects of high glucose and thiamine on the balance between matrix metalloproteinases and their tissue inhibitors in vascular cells

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Abstract

Pericyte survival in diabetic retinopathy depends also on interactions with extracellular matrix (ECM) proteins, which are degraded by matrix metalloproteinases (MMP). Elevated glucose influences ECM turnover, through expression of MMP and their tissue inhibitors, TIMP. We reported on reduced pericyte adhesion to high glucose-conditioned ECM and correction by thiamine. We aimed at verifying the effects of thiamine and benfotiamine on MMP-2, MMP-9 and TIMP expression and activity in human vascular cells with high glucose. In HRP, MMP-2 activity, though not expression, increased with high glucose and decreased with thiamine and benfotiamine; TIMP-1 expression increased with high glucose plus thiamine and benfotiamine; MMP-9 was not expressed. In EC, MMP-9 and MMP-2 expression and activity increased with high glucose, but thiamine and benfotiamine had no effects; TIMP-1 expression was unchanged. Neither glucose nor thiamine modified TIMP-2 and TIMP-3 expression. TIMP-1 concentrations did not change in either HRP or EC. High glucose imbalances MMP/TIMP regulation, leading to increased ECM turnover. Thiamine and benfotiamine correct the increase in MMP-2 activity due to high glucose in HRP, while increasing TIMP-1.

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Acknowledgments

This work was supported by grants from the Compagnia di San Paolo, Turin, Italy. E. Beltramo was the recipient of the 2002 European Association for the Study of Diabetes (EASD)/Eli Lilly Research Fellowship in Diabetes Microvascular Complications.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy

    Sonia Tarallo, Elena Beltramo, Elena Berrone, Patrizia Dentelli & Massimo Porta

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  1. Sonia Tarallo
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  2. Elena Beltramo
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  3. Elena Berrone
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  4. Patrizia Dentelli
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  5. Massimo Porta
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Correspondence to Sonia Tarallo.

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Tarallo, S., Beltramo, E., Berrone, E. et al. Effects of high glucose and thiamine on the balance between matrix metalloproteinases and their tissue inhibitors in vascular cells. Acta Diabetol 47, 105–111 (2010). https://doi.org/10.1007/s00592-009-0124-5

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  • DOI: https://doi.org/10.1007/s00592-009-0124-5

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